Andes Virus DNA Vaccine for the Prevention of Hantavirus Pulmonary Syndrome Using the PharmaJet Stratis(R) Needle-Free Injection Delivery Device

NCT03682107 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 16-0119HHSN272201300016I
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, placebo controlled, double-blind, dose escalation trial of 48 males and non-pregnant females, 18-49 years old, inclusive, who are in good health and meet all eligibility criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of an Andes Virus (ANDV) DNA vaccine for the prevention of Hantavirus Pulmonary Syndrome (HPS). ANDV DNA vaccine or placebo will be administered using the PharmaJet Stratis(R) Needle-Free Injection System. The study duration is 23 months while the subject participation duration is 12 months. Subjects assigned to the 3 dose regimen will receive ANDV DNA vaccine on Days 1, 29 and 169, and placebo on Day 57. Subjects assigned to the 4 dose regimen will receive ANDV DNA on Days 1, 29, 57 and 169. Two doses (2 or 4 mg) of ANDV DNA vaccine will be evaluated. The primary objective of this study is to assess the safety and reactogenicity of the ANDV DNA vaccine by dosage cohort and treatment arm when administered using the PharmaJet Stratis(R) Needle-Free Injection system in normal, healthy adults.

Conditions

Hantavirus Pulmonary Infection; Immunisation

Keywords

Andes Virus DNA; ANDV DNA; Hantavirus; Immunogenicity; PharmaJet Stratis; Pulmonary Syndrome; Safety; Vaccine

Outcome Measures

Primary Outcomes (13)

• Number of Participants Experiencing Clinical Safety Laboratory Adverse Events

  Laboratory parameters include alanine aminotransferase (ALT), total bilirubin, creatinine, blood urea nitrogen (BUN), hemoglobin, absolute neutrophil count (ANC), sodium, potassium, white blood cells (WBC), and platelet count. Laboratory results were considered adverse events using the following thresholds: ALT 50 IU/L or greater; total bilirubin 1.30 mg/dL or greater; creatinine 0.81 mg/dL or greater (female) or 1.11 mg/dL or greater (male); BUN 24 mg/dL or greater; hemoglobin 11.6 g/dL or lower (female) or 13.2 g/dL or lower (male); ANC \<1.8 K/mcL; sodium 135 mmol/L or lower (decrease) or 146 mmol/L or greater (increase); potassium 3.0 mmol/L or lower (decrease) or 5.2 mmol/L or greater (increase); WBC 4.4 K/mcL or lower (decrease) or 13.1 K/mcL or greater (increase 18 to \<21 years) and 11.1 K/mcL or greater (increase 21 years or older); or platelets 134 K/mcL or below (decrease) or 467 K/mcL or greater (increase).

  Day 8, Day 36, Day 64, Day 176

• Number of Participants Reporting Serious Adverse Events (SAEs) From Day 1 Through Day 337

  An adverse event was considered serious if it resulted in any of the following outcomes: death, a life-threatening adverse event (its occurrence places the participant at immediate risk of death), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Adverse events can be considered serious when they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

  Day 1 through Day 337

• Number of Participants Reporting Vaccine-Related Serious Adverse Events (SAEs) From Day 1 Through Day 337

  An adverse event is considered serious if it results in any of the following outcomes: death, a life-threatening adverse event (its occurrence places the participant at immediate risk of death), inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Adverse events can be considered serious when they may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition. An adverse event was considered related to the study product if there was a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.

  Day 1 through Day 337

• Number of Participants Experiencing Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197

  Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of first study vaccination through 28 days after the last study vaccination or after Day 169 if the fourth vaccination wasn't received.

  Day 1 through Day 197

• Number of Participants Experiencing Vaccine-Related Unsolicited Non-Serious Adverse Events at Any Time From Day 1 to Day 197

  Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of first study vaccination through 28 days after the last study vaccination or after Day 169 if the fourth vaccination wasn't received. An adverse event was considered related to the study product if there was a reasonable possibility that the study product caused the adverse event. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event.

  Day 1 through Day 197

• Number of Participants Reporting Solicited Local Adverse Events From Day 1 Through Day 8

  Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the first vaccination.

  Day 1 through Day 8

• Number of Participants Reporting Solicited Local Adverse Events From Day 29 Through Day 36

  Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the second vaccination.

  Day 29 through Day 36

• Number of Participants Reporting Solicited Local Adverse Events From Day 57 Through Day 64

  Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement (measuring \>0mm), induration, induration measurement (measuring \>0mm), skin discoloration, ecchymosis, and ecchymosis measurement (measuring \>0mm). Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the third vaccination.

  Day 57 through Day 64

• Number of Participants Reporting Solicited Local Adverse Events From Day 169 Through Day 176

  Local adverse events solicited on a memory aid provided to participants included pain, tenderness, erythema, erythema measurement, induration, induration measurement, skin discoloration, ecchymosis, and ecchymosis measurement. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the fourth vaccination.

  Day 169 through Day 176

• Number of Participants Reporting Solicited Systemic Adverse Events From Day 1 Through Day 8

  Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the first vaccination.

  Day 1 through Day 8

• Number of Participants Reporting Solicited Systemic Adverse Events From Day 29 Through Day 36

  Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the second vaccination.

  Day 29 through Day 36

• Number of Participants Reporting Solicited Systemic Adverse Events From Day 57 Through Day 64

  Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the third vaccination.

  Day 57 through Day 64

• Number of Participants Reporting Solicited Systemic Adverse Events From Day 169 Through Day 176

  Systemic adverse events solicited on a memory aid provided to participants included feverishness, malaise, fatigue, myalgia, headache, nausea, dizziness, and fever. Participants were considered to have experienced the AE if they reported an event of mild or greater severity on any of the 7 days following the fourth vaccination. Systemic AEs were considered mild severity if they were noticeable but did not interfere with daily activity; events (other than headache) were considered moderate severity if they interfered with daily activity; events (other than headache) were considered severe severity if they caused significant interference and prevented daily activity. Headache events were considered moderate severity if they required any use of pain reliever or interfered with daily activity; headache events were severe if they prevented daily activity or required use of a prescription medication.

  Day 169 through Day 176

Secondary Outcomes (6)

• Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Plaque Reduction Neutralization Titers

  Day 1, Day 57, Day 85, Day 197

• Geometric Mean Titers (GMTs) of Neutralizing Antibodies to ANDV Measured by Pseudovirion Neutralization Titers

  Day 1, Day 57, Day 85, Day 197

• Number of Participants With ANDV Antibody Titers Greater Than or Equal to 20 as Measured by Plaque Reduction Neutralization Titers

  Day 57, Day 85, Day 197

• Number of Participants With ANDV Antibody Titers Greater Than or Equal to 20 as Measured by Pseudovirion Neutralization Titers

  Day 57, Day 85, Day 197

• Percentage of Participants Achieving ANDV Antibody Seroconversion as Measured by Plaque Reduction Neutralization Titers

  Day 57, Day 85, Day 197

Study Arms (4)

Arm 1 (2 mg ANDV - 3-dose regimen)

EXPERIMENTAL

1 sentinel subject assigned to the 3-dose regimen will receive 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine on Days 29, 169, and matching placebo on Day 57 in double-blind manner. 11 subjects assigned to the 3-dose regimen will receive either 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 169, and matching placebo on Day 57 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Biological: Andes virus DNA vaccine; Other: Placebo

Arm 2 (2 mg ANDV - 4-dose regimen)

EXPERIMENTAL

1 sentinel subject assigned to the 4-dose regimen will receive 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and Days 29, 57 and 169 in double-blind manner. 11 subjects assigned to the 4-dose regimen will receive either 2 mg (2 injections of 0.5 ml (1 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 57 and 169 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Biological: Andes virus DNA vaccine; Other: Placebo

Arm 3 (4 mg ANDV - 3-dose regimen)

EXPERIMENTAL

1 sentinel subject assigned to the 3-dose regimen will receive 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine on Days 29, 169, and matching placebo on Day 57 in double-blind manner. 11 subjects assigned to the 3-dose regimen will receive either 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 169, and matching placebo on Day 57 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Biological: Andes virus DNA vaccine; Other: Placebo

Arm 4 (4 mg ANDV - 4-dose regimen)

EXPERIMENTAL

1 sentinel subject assigned to the 4-dose regimen will receive 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Day 1 in an open label manner, and Days 29, 57 and 169 in double-blind manner. 11 subjects assigned to the 4-dose regimen will receive either 4 mg (2 injections of 0.5 ml (2 mg/0.5 ml each)) of ANDV DNA vaccine intramuscularly into the left and right deltoid on Days 1, 29, 57 and 169 (n=9) or matching placebo on Days 1, 29, 57, and 169 (n=2).

Biological: Andes virus DNA vaccine; Other: Placebo

Interventions

Andes virus DNA vaccine BIOLOGICAL

A vaccine targeting the hantavirus pulmonary syndrome (HPS) causative agent Andes Virus (ANDV), with potential pan-hantavirus effect. The plasmid backbone, pWRG7077, is modified to produce the active ingredient of the vaccine, plasmid pWRG/AND-M (opt2), and includes the ANDV M gene responsible for encoding viral GnGc envelope glycoproteins. ANDV DNA vaccine will be administered intramuscularly at 2 mg or 4 mg doses using the PharmaJet Stratis Needle-Free Injection System.

Arm 1 (2 mg ANDV - 3-dose regimen); Arm 2 (2 mg ANDV - 4-dose regimen); Arm 3 (4 mg ANDV - 3-dose regimen); Arm 4 (4 mg ANDV - 4-dose regimen)

Placebo OTHER

Normal saline injections will be administered intramuscularly as matching placebo using the PharmaJet Stratis Needle-Free Injection System

Arm 1 (2 mg ANDV - 3-dose regimen); Arm 2 (2 mg ANDV - 4-dose regimen); Arm 3 (4 mg ANDV - 3-dose regimen); Arm 4 (4 mg ANDV - 4-dose regimen)

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent before initiation of any study procedures.
• Are able to understand and comply with planned study procedures and be available for all study visits/phone calls.
• Males or non-pregnant females ages 18-49, inclusive.

You may not qualify if:

• Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).
• Pulse is 47 to 105 beats per minute (bpm), inclusive.
• Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive.
• Diastolic blood pressure (BP) is 55 to 95 mm Hg, inclusive.
• Have acceptable screening laboratories\* within 28 days prior to enrollment. \*Screening laboratory values that are outside acceptable range but are thought to be due to an acute condition or due to laboratory error may be repeated once.
• Urine protein screen is negative or trace.
• Drug screen for opiates is negative.
• HgbA1C \< 6.3% at screening.
• HIV - 1/2 antibody negative.
• HCV antibody negative.
• HBsAg negative.
• Women of childbearing potential\*, must be using an effective method of contraception\*\* from 30 days prior to the first study vaccination until 90 days after the last study vaccination.
• \*Women of childbearing potential are defined as those who have not been sterilized via tubal ligation, bilateral oophorectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with history of documented radiological confirmation test at least 90 days after the procedure (or with use of another birth control method if history of confirmation test not confirmed), AND are still menstruating or \< 1 year since the last menses if perimenoapausal.
• \*\*For this study, we define an effective contraceptive method as one that results in a failure rate of less than 1% per year when it is used consistently and correctly. This includes, but is not limited to, non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with a vasectomized partner, male condoms with the use of applied spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
• Women of childbearing potential\* must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours prior to each study vaccination.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center - Infectious Diseases

Cincinnati, Ohio, 45229-3039, United States

Location

Related Publications (1)

• Paulsen GC, Frenck R Jr, Tomashek KM, Alarcon RM, Hensel E, Lowe A, Brocato RL, Kwilas SA, Josleyn MD, Hooper JW. Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study. J Infect Dis. 2024 Jan 12;229(1):30-38. doi: 10.1093/infdis/jiad235.

  PMID: 37380156 DERIVED

MeSH Terms

Conditions

Hantavirus Pulmonary Syndrome

Condition Hierarchy (Ancestors)

Hantavirus Infections; Bunyaviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Insufficiency; Respiration Disorders; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Grant Paulsen
• Organization: Cincinnati Children's Hospital

Grant.Paulsen@cchmc.org

513-636-4578

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2018
• First Posted: September 24, 2018
• Study Start: February 19, 2019
• Primary Completion: September 23, 2020
• Study Completion: September 23, 2020
• Last Updated: November 22, 2022
• Results First Posted: October 14, 2021

Record last verified: 2021-04-06

Locations

US (1)